scholarly journals Constitutive expression of bcl-2 in B cells causes a lethal form of lupuslike autoimmune disease after induction of neonatal tolerance to H-2b alloantigens.

1996 ◽  
Vol 183 (6) ◽  
pp. 2523-2531 ◽  
Author(s):  
M López-Hoyos ◽  
R Carrió ◽  
R Merino ◽  
L Buelta ◽  
S Izui ◽  
...  
Keyword(s):  
B Cells ◽  
Autoimmune Disease ◽  
Constitutive Expression ◽  
Systemic Autoimmune Disease ◽  
Spleen Cells ◽  
Term Survival ◽  
F1 Hybrid ◽  
Wide Range

The bcl-2 protooncogene has been shown to provide a survival signal to self-reactive B cells, but it fails to override their developmental arrest after encounter with antigen. Furthermore, constitutive expression of bcl-2 in B cells does not promote the development of autoimmune disease in most strains of mice, indicating that signals other than those conferred by bcl-2 are required for long-term survival and differentiation of self-reactive B cells in vivo. To further examine the factors that are required for the pathogenesis of autoimmune disease, we have assessed the effect of bcl-2 overexpression on the development of host-versus-graft disease, a self-limited model of systemic autoimmune disease. In this model, injection of spleen cells from (C57BL/6 x BALB/c)F1 hybrid mice into BALB/c newborn parental mice induces immunological tolerance to donor tissues and activation of autoreactive F1 donor B cells through interactions provided by allogeneic host CD4+ T cells. BALB/c newborns injected with spleen cells from (C57BL/6 x BALB/c)F1 mice expressing a bcl-2 transgene in B cells developed high levels of anti-single-stranded DNA and a wide range of pathogenic autoantibodies that were not or barely detectable in mice injected with nontransgenic spleen cells. In mice injected with transgenic B cells, the levels of pathogenic autoantibodies remained high during the course of the study and were associated with long-term persistence of donor B cells, development of a severe autoimmune disease, and accelerated mortality. These results demonstrate that bcl-2 can provide survival signals for the maintenance and differentiation of autoreactive B cells, and suggest that both increased B cell survival and T cell help play critical roles in the development of certain forms of systemic autoimmune disease.

scholarly journals Partial Decellularization for Segmental Tracheal Scaffold Tissue Engineering: A Preliminary Study in Rabbits

Biomolecules ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 866
Author(s):  
Luong Huu Dang ◽  
Yuan Tseng ◽  
How Tseng ◽  
Shih-Han Hung
Keyword(s):  
Mechanical Stability ◽  
Vital Staining ◽  
Potential Method ◽  
Term Survival ◽  
Long Term Survival ◽  
Cartilage Cells ◽  
Preliminary Study ◽  
Epithelial Layers

In this study, we developed a new procedure for the rapid partial decellularization of the harvested trachea. Partial decellularization was performed using a combination of detergent and sonication to completely remove the epithelial layers outside of the cartilage ring. The post-decellularized tracheal segments were assessed with vital staining, which showed that the core cartilage cells remarkably remained intact while the cells outside of the cartilage were no longer viable. The ability of the decellularized tracheal segments to evade immune rejection was evaluated through heterotopic implantation of the segments into the chest muscle of rabbits without any immunosuppressive therapy, which demonstrated no evidence of severe rejection or tissue necrosis under H&E staining, as well as the mechanical stability under stress-pressure testing. Finally, orthotopic transplantation of partially decellularized trachea with no immunosuppression treatment resulted in 2 months of survival in two rabbits and one long-term survival (2 years) in one rabbit. Through evaluations of posttransplantation histology and endoscopy, we confirmed that our partial decellularization method could be a potential method of producing low-immunogenic cartilage scaffolds with viable, functional core cartilage cells that can achieve long-term survival after in vivo transplantation.

scholarly journals Long-Term Survival and Gradual Recovery of B Cells in Patients (Pts) with Refractory Large B Cell Lymphoma (LBCL) Treated with Axicabtagene Ciloleucel (Axi-Cel)

2021 ◽  
Vol 27 (3) ◽  
pp. S404-S405
Author(s):  
Caron A. Jacobson ◽  
Frederick L. Locke ◽  
Armin Ghobadi ◽  
David B. Miklos ◽  
Lazaros J. Lekakis ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Term Survival ◽  
Long Term Survival ◽  
Large B Cell Lymphoma ◽  
Large B Cell

scholarly journals A Replication-Defective Gammaherpesvirus Efficiently Establishes Long-Term Latency in Macrophages but Not in B Cells In Vivo

2008 ◽  
Vol 82 (17) ◽  
pp. 8500-8508 ◽  
Author(s):  
Haiyan Li ◽  
Kazufumi Ikuta ◽  
John W. Sixbey ◽  
Scott A. Tibbetts
Keyword(s):  
B Cells ◽  
Viral Genome ◽  
Lytic Replication ◽  
Mutant Virus ◽  
Wild Type Virus ◽  
Type Virus ◽  
Wild Type ◽  
Virus Latency

ABSTRACT Murine gammaherpesvirus 68 (γHV68 or MHV68) is genetically related to the human gammaherpesviruses Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV), providing a useful system for in vivo studies of the virus-host relationship. To begin to address fundamental questions about the mechanisms of the establishment of gammaherpesvirus latency, we previously generated a replication-defective γHV68 lacking the expression of the single-stranded DNA binding protein encoded by orf6. In work presented here, we demonstrate that this mutant virus established a long-term infection in vivo that was molecularly identical to wild-type virus latency. Thus, despite the absence of an acute phase of lytic replication, the mutant virus established a chronic infection in which the viral genome (i) was maintained as an episome and (ii) expressed latency-associated, but not lytic replication-associated, genes. Macrophages purified from mice infected with the replication-defective virus harbored viral genome at a frequency that was nearly identical to that of wild-type γHV68; however, the frequency of B cells harboring viral genome was greatly reduced in the absence of lytic replication. Thus, this replication-defective gammaherpesvirus efficiently established in vivo infection in macrophages that was molecularly indistinguishable from wild-type virus latency. These data point to a critical role for lytic replication or reactivation in the establishment or maintenance of latent infection in B cells.

scholarly journals From young massive star clusters to old globulars: long-term survival chances

2006 ◽  
Vol 2 (S237) ◽  
pp. 408-408
Author(s):  
Richard de Grijs
Keyword(s):  
Galaxy Formation ◽  
Massive Star ◽  
Cluster Formation ◽  
Star Clusters ◽  
Term Survival ◽  
Star Forming ◽  
Distant Galaxies ◽  
Wide Range ◽  
Galaxy Collisions

Young, massive star clusters (YMCs) are the most notable and significant end products of violent star-forming episodes triggered by galaxy collisions and close encounters. The question remains, however, whether or not at least a fraction of the compact YMCs seen in abundance in extragalactic starbursts, are potentially the progenitors of (≳10 Gyr) old globular cluster (GC)-type objects. If we could settle this issue convincingly, one way or the other, the implications of such a result would have far-reaching implications for a wide range of astrophysical questions, including our understanding of the process of galaxy formation and assembly, and the process and conditions required for star (cluster) formation. Because of the lack of a statistically significant sample of YMCs in the Local Group, however, we need to resort to either statistical arguments or to the painstaking approach of case-by-case studies of individual objects in more distant galaxies.

DIAGNOSTIC MARKERS OF ANTIPHOSPHOLIPID SYNDROME

2021 ◽  
Vol 2 (1) ◽  
pp. 5-10
Author(s):  
Galyamova K.I.
Keyword(s):  
Autoimmune Disease ◽  
Antiphospholipid Syndrome ◽  
Pregnancy Complications ◽  
Main Part ◽  
Diagnostic Markers ◽  
Systemic Autoimmune Disease ◽  
Term Study ◽  
Long Term Study ◽  
In Cells

Antiphospholipid syndrome is a systemic autoimmune disease, the main part of pathogenesis of which is induc-tion of an inflammatory and procoagulant state in cells, thrombosis of venous and/or arterial vessels and, as a consequence, pregnancy complications. [4] Despite the long-term study of this pathology, the mechanism of its development is still not fully understood, what makes it more difficult to diagnose, prevent and treat this disease and to assess the risks of its complications.

Correlation between magnesium and potassium contents in muscle: role of Na(+)-K+ pump

1993 ◽  
Vol 264 (2) ◽  
pp. C457-C463 ◽  
Author(s):  
I. Dorup ◽  
T. Clausen
Keyword(s):  
Extensor Digitorum Longus ◽  
Extensor Digitorum ◽  
Deficient Diet ◽  
Young Rats ◽  
Wide Range ◽  
86Rb Influx

In young rats fed a Mg(2+)-deficient diet for 3 wk, Mg2+ and K+ contents in soleus and extensor digitorum longus muscles were significantly reduced and closely correlated. In isolated soleus muscles, Mg2+ depletion induced an even more pronounced loss of K+, and Mg2+ and K+ contents were correlated over a wide range (r = 0.95, P < 0.001). Extracellular Mg2+ (0-1.2 mM) caused no change in total or ouabain-suppressible 86Rb influx. After long-term incubation in Ca(2+)-Mg(2+)-free buffer with EDTA and EGTA, cellular Mg2+ and K+ contents were reduced by 35 and 15%, respectively, without any reduction in ATP and total or ouabain-suppressible 86Rb influx. In Mg(2+)-depleted muscles 42K efflux was increased by up to 42%, and repletion with Mg2+ produced a graded decrease. We conclude that Mg2+ and K+ contents are closely correlated in muscles Mg2+ depleted in vivo or in vitro and that neither extracellular nor moderate intracellular Mg2+ depletion affects total or Na(+)-K+ pump-mediated K+ influx. The reduced K+ content may rather be related to increased K+ efflux from the muscles.

scholarly journals B cell–intrinsic TLR signals amplify but are not required for humoral immunity

2007 ◽  
Vol 204 (13) ◽  
pp. 3095-3101 ◽  
Author(s):  
Almut Meyer-Bahlburg ◽  
Socheath Khim ◽  
David J. Rawlings
Keyword(s):  
B Cells ◽  
B Cell ◽  
Long Term Memory ◽  
Altered Expression ◽  
Intrinsic Signals ◽  
Antibody Titers ◽  
Specific Igg ◽  
B Cell Subsets

Although innate signals driven by Toll-like receptors (TLRs) play a crucial role in T-dependent immune responses and serological memory, the precise cellular and time-dependent requirements for such signals remain poorly defined. To directly address the role for B cell–intrinsic TLR signals in these events, we compared the TLR response profile of germinal center (GC) versus naive mature B cell subsets. TLR responsiveness was markedly up-regulated during the GC reaction, and this change correlated with altered expression of the key adaptors MyD88, Mal, and IRAK-M. To assess the role for B cell–intrinsic signals in vivo, we transferred MyD88 wild-type or knockout B cells into B cell–deficient μMT mice and immunized recipient animals with 4-hydroxy-3-nitrophenylacetyl (NP) chicken gamma globulin. All recipients exhibited similar increases in NP-specific antibody titers during primary, secondary, and long-term memory responses. The addition of lipopolysaccharide to the immunogen enhanced B cell-intrinsic, MyD88-dependent NP-specific immunoglobulin (Ig)M production, whereas NP-specific IgG increased independently of TLR signaling in B cells. Our data demonstrate that B cell–intrinsic TLR responses are up-regulated during the GC reaction, and that this change significantly promotes antigen-specific IgM production in association with TLR ligands. However, B cell–intrinsic TLR signals are not required for antibody production or maintenance.

scholarly journals IMMUNOLOGIC REACTIONS TO HAPTENS ON AUTOLOGOUS CARRIERS

1973 ◽  
Vol 137 (2) ◽  
pp. 411-423 ◽  
Author(s):  
John W. Moorhead ◽  
Curla S. Walters ◽  
Henry N. Claman
Keyword(s):  
T Cells ◽  
B Cells ◽  
Aminocaproic Acid ◽  
Single Amino Acid ◽  
Secondary Response ◽  
Spleen Cells ◽  
Activated T Cells ◽  
Thymus Cells

Both thymus-derived (T) and bone marrow-derived (B) lymphocytes participate in the response to a hapten 4-hydroxy-3-iodo-5-nitrophenylacetic acid (NIP), coupled to a nonimmunogenic isologous carrier, mouse gamma globulin (MGG). Spleen cells from mice immunized with NIP-MGG show increased DNA synthesis in vitro when cultured with NIP-MGG. The participation of and requirement for T cells in the response was demonstrated by treating the spleen cells with anti-θ serum. This treatment resulted in a 77% inhibition of the antigen response. Furthermore, adoptively transferred normal thymus cells could be specifically "activated" by NIP-MGG in vivo and they responded secondarily to the antigen in vitro. The active participation of B cells in the secondary response was demonstrated by passing the immune spleen cells through a column coated with polyvalent anti-MGG serum. Column filtration reduced the number of NIP-specific plaque-forming cells and NIP-specific rosette-forming cells (both functions of B cells) and produced a 47% inhibition of the NIP-MGG response. The ability of the cells to respond to phytohemagglutinin (PHA) was not affected by column filtration showing that T cells were not being selectively removed. The participation of B cells in the in vitro NIP-MGG response was also shown by treatment of the spleen cells with antiserum specific for MGG and MGG determinants. B cells were removed by treatment with anti-IgM or polyvalent anti-MGG serum plus complement, resulting in a respective 46 and 49% inhibition of the response to NIP-MGG. (Treatment with anti-IgM serum had no effect on T cells.) The contribution of the hapten NIP to stimulation of T cells was investigated using NIP-MGG-activated thymus cells. These activated T cells responded in vitro very well to the NIP-MGG complex but not to the MGG carrier alone demonstrating the requirement of the hapten for T cell stimulation. The response was also partially inhibited (41%) by incubating the activated cells with NIP coupled to a single amino acid (epsilon-aminocaproic acid) before addition of NIP-MGG. These results demonstrated that T cells recognize the hapten NIP when it is coupled to the isologous carrier MGG.

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